The overall objective of this proposal is to gain a more complete understanding of the pathologic alterations which occur between magnocellular cholinergic neurons and galanin containing interneurons and their processes within the basal forebrain of human normal aged, Alzheimer's (AD) and Parkinson's (PD) dementia individuals. Since galanin is inhibitory to acetylcholine, it has been hypothesized that hyperinnervation by galanin containing profiles upon nucleus basalis cholinergic neurons in AD and PD may play a key role in the degenerative process(es) underlying cholinergic cell dysfunction in these neurodegenerative disorders. To evaluate this hypothesis we will 1) determine the cellular location of mRNA for galanin synthesis within the human basal forebrain subfields, 2) determine whether the expression of galanin mRNA parallels the species difference between human and monkeys we reported for the peptide galanin within the basal forebrain (36), 3) determine whether other basal forebrain cell types not currently known to contain the peptide galanin express its mRNA, 40 determine whether galanin hyperinnervation to the cholinergic basal forebrain neurons occurs in all subfields of this region in Alzheimer's and Parkinson's dementia, 5) determine whether the hyperinnervation of galanin profiles within the nucleus basalis is accompanied by an over expression of galanin mRNA, and 6) determine whether the basal forebrain hypertrophic galanin containing profiles innervate ALZ-50 expressing elements. The planned studies will utilize immunohistochemistry using a polyclonal galanin antibody, an IgM mouse monoclonal ALZ-50 antibody and galanin mRNA in situ hybridization. The data generated from this proposal will provide much needed information concerning the neurodegenerative events which may play a pivotal role in basal forebrain cholinergic degeneration in Alzheimer's and Parkinson's dementias. Furthermore, these data may suggest avenues for the development of new pharmacological therapies as a means of retarding intellectual deterioration in dementia.